Many therapeutic proteins are normal human proteins. For example, interleukin-2, erythropoietin, and growth hormone are all human proteins that are given to humans who already usually make endogenous levels of these proteins. In general, immune responses against completely normal human proteins are rare when these proteins are used as therapeutics.
Recently it has become apparent that many fusion proteins with artificial activities are useful as therapeutic proteins. For example, Enbrel is a fusion of the extracellular domain of a TNF receptor with an IgG1 Fc region. Enbrel is used to treat rheumatoid arthritis, and is thought to function by titrating TNF and preventing TNF action. However, a significant incidence of anti-Enbrel antibodies have been noted in patients treated with Enbrel.
Another example of a therapeutically useful class of fusion proteins is the immunocytokines. These proteins include an antibody moiety and a cytokine moiety, and are useful for targeting cytokines to diseased cells, such as cancer cells. However, the therapeutic use of many of these fusion proteins is curtailed due to their immunogenicity in mammals, especially humans.
Therefore, there is a need to generate fusion proteins with reduced immunogenicity in order to use these proteins in therapy.